~..- ,}'Nrz'1nopr.niscair.res.in/bitstream/123456789/49175/1/IJCA 22A...w hich ere filtered off and was ed wi the anol and dried in vacuo over P4010• The magnetic susceptibility

Indian Journa~ of ChemistryVol. 22A, March 1983, pp 267-269

Planar NickeI(II) & Copper(II) Complexesof otential Antimalarial Drugs, N\ N4_Disubstituted Thio & Selenosemicarba-

~ones of 2-Acetylpyridine

YUDHVIR K BHOON*

Chemis ry Department, Sri Venkateswara College,haula Kuan, New Delhi 110021

and

mHN P SCOVILL & DANIEL L KLAYMANI .

Walter Reed Army Institute of Research.DiY

1

ision of Experimental Therapeutics,Washington, D.C. 20012, USA

Recei ed 11 June 1982; revised and accepted 12 November 1982

Complexes J the general composition MIl(SAm)X and MIl(SeAm)X (M;:rCu. i; SAm-H and SeAm-H are thio andse1enosemicarbazone derivatives respectively of 2-acetylpyridine;and -CI-, B~-, 1-, OAc- or NO.) have been isolated andcharacterized ~n the basis of magnetic and spectral measure-ments. Plana geometry is assigned to all the complexes.

Thiosemicarbazones belong to a special class ofchela ing molecules which possess a wide range ofmedicinal prppertlesl-4• 2-Acetylpyndine-4-phenyl-3-thiosemicar~azone has shown antimalarial activityand a seires of mono and disubstituted (at N4) thio-semicarbazones have been recently synthesized toknow about the molecular features essential for anti-mala ial andlantileukemic activitiesv", From these stu-dies, it was inferred that among the compounds whereN4 atom waslincorporated into a six or seven-memberedring such as piperidine, piperizine or azabicyclo [3,2,2]nonane system, the potency was manifold. Amongsuch compounds, 3-azabicyclo[3,2,2]nonane-3-thio-carboxylic acid-2[(I-(2-pyridyl)ethylidene)] hydra-zide, I, has been found to be not only the mostpoten; ial a timalarial drug but it also possessesantileukemic propertiesv'", Since the biologicalactivity of such type of compounds is thought to bedue to their potential chelating+" behaviour with thetrace elements, we have initiated studies on thetransition metal complexes of (I) and its seleniumanalogue, Se1\m-H, II.

The prese t note describes the preparation andcharacterizat on of copper(II) and nickel(II) com-plexes of SAm-Hand SeAm-H by magnetic and spect-ral measurements. All the compounds have beenassig ed square-planar geometry.

The 3Jazabicyclo[3,2,2]nonane- 3-thiocarbox ylicacid-2-[1-(2-~yridyl)ethylidene] hydrazide, SAm-H andits selenium analogue-Se/vm-H were prepared (by therepor ed methods=" and were recrystallized frommethyl aleoh 1.

~..-",,"}'Nrz'1cH:3 ~ '-J)

n,SeAm-H

Preparation of comp/exes-Copper(U) complexes ofSAm-H and SeAm-H were easily prepared by addingthe ethanolic solution of the appropriate copper(II)salt to the boiling ethanolic solution of the ligand inequimolar ratio. In the case of iodo complexes, anammonical solution of cuprous iodide was added tothe ligand solution. In each case, the yellow colourof the ligand solution changed to dark-brown; thesolution was allowed to crystallize by slow evapo-ration. After several days, dark crystalline andshining compounds separated out which were filteredoff and recrystallized again from ethanol.

In the case of nickel(II) complexes, however, redneedle shaped crystalline compounds separated outwhich were filtered off and washed with ethanol anddried in vacuo over P4010•

The magnetic susceptibility measurements werecarried out at room temperature using the Faradaymethod with Hg[Co(CNS)4] as the calibrant. Theabsorption spectra of the complexes were recorded innujol mull on a DMR-21 spectrophotometer, andinfrared spectra were recorded in KBr on a PE-621Grating IR spectrophotometer.

From the analytical data (Table 1), it is obviousthat all the complexes are of 1 : 1 (metal: ligand)type. The magnetic moments of the copper(II) com-plexes (Table 1) are in the range 1.75-1.90 B. M. asexpected for mononuclear planar copper(II) com-pIexes8-12. All the nickel(II) complexes are diamagneticand hence planar geometry can be easily assigned tonickel(II) complexes.

The ligand SAm-His present in the thione from asshown by its PMR spectrum. A signal at M.23 isobserved due to the N-H proton. The absence of anylow-field signal also favours this formulation. Sucha molecule is expected to have electronic absorptionbands mainly arising from n-'lt* transitions of C=Sand C=N parts of the molecule. SAm-H showsbands at 25510 and 31250 cm-1 in chloroform solutionwhich may be assigned to n-'lt* and 'It-7t* transitionsrespectively. The selenium analogue, SeAm-H, showsa band at 27550 cnr? due to n-ts" transition.

The blue shift of n-'lt* transition in SeAm-H could

267

INDIAN J. CHEM., VOL. 22A, MARCH 1983

Table l-e-Elemental Analyses and Magnetic Moment Datafor the Complexes

Compound Found (Calc.), % (Le!! (B.-. --------- M.) at

M C N H 298K

SAm-H 63.57 18.54 7.28(63.31) (18.61) (7.14)

SeAm-H 55.01 16.04 6.30(54.84) (15.83) (6.14)

[CuIl(SAm) en 15.84 47.87 13.96 5.23 1.80(J 5.74) (47.63) (13.74) (5.01 )

[CuII(SAm) Br] 14.29 43.20 12.60 4.72 1.96(14.04) (43.14) (12.48) (4.68)

[CulI(SAm) I] 12.93 39.07 11.40 4.27 1.75(12.84) (38.64) (I 1.25) (4.14)

[CuII(SAm) OAc] 15.00 50.99 13.22 5.66 1.90(14.86) (50.78) (13.08) (5.48)

[CuII(SAm) N03] 15.33 46.32 13.51 5.06 1.87(15.18) (46.18) (J 3.44) (4.94)

[CuII(SeAm) CI] 14.18 42.86 12.5 4.69 1.78(14.04) (42.74) (12.43) (4.56)

[CulI(SeAm) BrJ 12.93 39.07 11.39 4.27 1.90(12.74) (38.93) (11.2 ) (4.14)

CulI(SeAm) I 11.80 35.66 10.40 1.86(11.67) (35.43) (10.28)

[CuIl(SeAm) OAcl 13.50 45.91 11.90 5.10 1.85(13.44) (45.67) (11.77) (5.04)

Table 2-PMR Spectral Data of SAm-H, SeAm-H and TheirNickel(II) Complexes (Chemical Shifts in 8 ppm)

Moiety SAm-H [NiII(SAm) SeAm-H [NiII(SeAm)Cll en

Terminal methy- 4.05-4.2d 3.90d 4.1-4.3d 3.85dlene protons

1.658 1.708 1.208Cyclic protons 1.658(methylene)

2.3-2.6' 2.188 2.68 2.148Methyl protonsC-H (terminal) 2.138 2.0-2.2 1.5-1.75dN-H 4.238 2.42dS/Se proton 15.28

s=singlet; d=doublet, t=triplet.

be possibly due to the presence of basic substituentNH2• on the C=Se moiety, which compensates theeffect of red shift expected in SeAm-H due to thehigher energy of nonbonding selenium orbital andlowering of the energy of,.; orbital due to smallerelectronegativity of selenium relative to sul-phur13-16,18.

SAm-H and SeAm-H chelate with metal ions in thethiol from as shown by IR studies". Thus, both n-,.*and ,.-,.* transitions of C=S and C=Se will be absentin the spectra of the complexes and bands due to ,.-,.*transitions of C=N group and ligand-metal shouldbe observed. These transitions have been found toappear at 22780 and 26460 cm-l respectively.

However, [CuII(SAm-H)CI] shows a very weakband at 16470 cm? (E = 158). The value of molarextinction coefficient of this band rules out its assign-ment as M-+L or L~M charge-transfer band, andhence it could possibly be the d_d19,20 band expectedfor planar coppertfl) complexes. This band appears

268

at higher energy (17860 cm-l, e=387) in he selepiumanalogue. Appearance of this band at h gher energy(17860 cm", e=387) and with greater in nsity in theselenium analogue is justified in view of the greaterligand-field strength of the selenium anI·logue com-pared to that of the sulphur compound.

The absorption spectra of other cop I er(H) com-plexes, recorded in nujol mull, show the -d band atdifferent positions and the complexes CO~d be arran-ged in the following order of decreasin. ligall(~-fieldstrengths: CulI(SeAm) F>CuIl(SeAm) OAc> CuIl-(SAm) (NOa) >CuII(SeAm) (N03»CuIl(~eAm) CI>CuII(SAm) CI>CulI(SeAm) Br>CuII(SA I ) BrACuJI(SeAm) I> CuII(SAm) I.

The nickel(lI) complexes do not show any bandbelow 10000 cm-1 in the absorption sdectra whichsupports their planar geometry as concluded fro I themagnetic susceptibility measurements. I

The PMR spectra of both the ligands have beenrecorded in CDCla and the results arelpresen~ed inTable 2. Only the aliphatic protons give well-definedsignals while the aromatic protons of ~yridine ringappear in both the spectra as ill-defined pea s dueperhaps to the stealing of intensity by aliphaticprotons of the bicyclo ring. An interdsting featureof the PMR spectrum of SeAm-H is thel appea~anceof a broad signal in the low-field regien (~15.~), inaddition to another peak at ~2.42 WhlC~ representsN-H proton. The low-field signal is of the rightntensity and position to represent Se-~.proton; thesignal could possibly arise due to the dY9amic equili-brium between the selenone(III) and sele I il(rV) ormsof SeAm-H.

Most of the peaks due to the aliphatic protons inthe ligands shift towards TMS position ~Inthe spectraof the corresponding nickel(II) cOl.nple~es, and thisshift could possibly be due to the presence of para-magnetic octahedral nickeI(I1) complexes in solutionphase due to the axial coordination! f the solventmolecules'" to the planar complex.

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464.

NOTES

15 Benson S W & Kistiakowsky G B, J Am chem Soc, 64(1942) 80.

16 Hosoya H, Tanaka J & Nagakura S, Bull chem Soc Japan,83 (1959) 850.

17 Saksena B D & Kagarise R E, J chem Phys, 19 (1951) 994.18 Bhoon Y K, Mitra S, ScoviII J P & Klayman D L, Trans

metal Chem, (in press).19 Raevskii 0 A, Shagidullin R R, Kitaev Yu P & Minkin

V I, Dokl Akad Nauk SSSR, 178 (1968) 112.20 Ali M Akbar, Livingstone S E & Phillinps D J, Inorg chim

Acta,S (1971) 493.21 Wayland B B & Wisniewski M D, J chem Soc, A17 (1971)

2727.

269